Bladder cancer accounts for approximately 8% and 6% of all new male cancers and 4% and 3% of male cancer deaths each year in the United Kingdom and the USA respectively (Silverman et al, 1999). Three quarters of all cases present as superficial disease and whilst half of these cases are cured by simple treatment, about half will develop recurrences (Gilbert et al, 1978). The field change theory of recurrence proposes that each recurrence has arisen de novo from a generalized precancerous urothelium (Raghavan et al, 1990;Harris and Neal, 1992). The clonal origin of recurrence (Sidransky et al, 1992;Habuchi et al, 1993;Chern et al, 1996) implies that either residual cells have been left at TURBT resulting in tumour recurrence at the original site or that intraluminal shedding and subsequent seeding occurs at the time of TURBT. There are several reports supporting this shedding and seeding hypothesis (Soloway and Masters, 1980;See et al, 1989;Rebel et al, 1994;Fadl-Elmula et al, 1999) and the effect of reduction in recurrence rate following intravesical instillation of various agents at the time of TURBT supports this concept (Lamm and Griffith, 1992). There is a clear need for models in which to investigate the process of bladder cancer seeding and invasion and also upon which to test potential therapeutic agents.The most commonly used models of invasion are the Boyden chamber and some form of matrigel assay. It is now clear that the extracellular matrix is more than a passive support but interacts with tumour cells regulating differentiation (Fujiyama et al, 1995;Scriven et al, 1997), proliferation (Southgate et al, 1994;Booth et al, 1997) and tumour angiogenesis (Vladovski et al, 1997). Likewise xenograft models are often technically difficult, with moderate levels of reproducibility and are more difficult to control. Therefore although these models have provided useful information (Cook and Hampton, 1997; Miyake et al, 1997) they are becoming inadequate.We have developed an in vitro model using de-epithelialized rat bladder onto which human bladder cancer cells are seeded, an analogous situation to seeding of cells at TURBT, and used this model to test potential mechanisms and therapeutic inhibitors of invasion.The plasminogen activator system regulates extracellular matrix degradation and is therefore critical in tumour cell implantation, invasion and metastasis (Conese and Blasi, 1995;Hudson and McReynolds, 1997). The most common plasminogen activator, urokinase plasminogen activator (uPA) functions via its receptor, urokinase plasminogen activator receptor (uPAR). High expression of both uPA and uPAR has been found to be of prognostic significance in a number of tumours including bladder (Hasui et al, 1994;Pedersen et al, 1994;Dickinson et al, 1995). Using this model we have investigated the effects of uPAR antagonists, suramin and N-acetylcysteine. The latter two are compounds thatHuman bladder cancer invasion model using rat bladder in vitro and its use to test mechanisms and therapeutic inhibitors of inva...